Wideband THz time domain spectroscopy based on optical rectification and electro-optic sampling

We present an analytical model describing the full electromagnetic propagation in a THz time-domain spectroscopy (THz-TDS) system, from the THz pulses via Optical Rectification to the detection via Electro Optic-Sampling. While several investigations deal singularly with the many elements that constitute a THz-TDS, in our work we pay particular attention to the modelling of the time-frequency behaviour of all the stages which compose the experimental set-up. Therefore, our model considers the following main aspects: (i) pump beam focusing into the generation crystal; (ii) phase-matching inside both the generation and detection crystals; (iii) chromatic dispersion and absorption inside the crystals; (iv) Fabry-Perot effect; (v) diffraction outside, i.e. along the propagation, (vi) focalization and overlapping between THz and probe beams, (vii) electro-optic sampling. In order to validate our model, we report on the comparison between the simulations and the experimental data obtained from the same set-up, showing their good agreement

Nuclearity of rapidly decreasing ultradifferentiable functions and time-frequency analysis

[EN] We use techniques from time-frequency analysis to show that the space S(omega )of rapidly decreasing omega-ultradifferentiable functions is nuclear for every weight function omega(t) = o(t) as t tends to infinity. Moreover, we prove that, for a sequence (M-p)(p) satisfying the classical condition (M1) of Komatsu, the space of Beurling type S-(M)p when defined with L-2 norms is nuclear exactly when condition (M2)' of Komatsu holds.We thank the reviewer very much for the careful reading of our manuscript and the comments to improve the paper. The first three authors were partially supported by the Project FFABR 2017 (MIUR), and by the Projects FIR 2018 and FAR 2018 (University of Ferrara). The first and third authors are members of the Gruppo Nazionale per l'Analisi Matematica, la Probabilita e le loro Applicazioni (GNAMPA) of the Istituto Nazionale di Alta Matematica (INdAM). The research of the second author was partially supported by the project MTM2016-76647-P and the grant BEST/2019/172 from Generalitat Valenciana. The fourth author is supported by FWF-project J 3948-N35.Boiti, C.; Jornet Casanova, D.; Oliaro, A.; Schindl, G. (2021). Nuclearity of rapidly decreasing ultradifferentiable functions and time-frequency analysis. Collectanea mathematica. 72(2):423-442. https://doi.org/10.1007/s13348-020-00296-0S423442722Asensio, V., Jornet, D.: Global pseudodifferential operators of infinite order in classes of ultradifferentiable functions. Rev. R. Acad. Cienc. Exactas Fís. Nat. Ser. A Mat. RACSAM 113(4), 3477–3512 (2019)Aubry, J.-M.: Ultrarapidly decreasing ultradifferentiable functions, Wigner distributions and density matrices. J. London Math. Soc. 2(78), 392–406 (2008)Björck, G.: Linear partial differential operators and generalized distributions. Ark. Mat. 6(21), 351–407 (1966)Boiti, C., Jornet, D., Oliaro, A.: Regularity of partial differential operators in ultradifferentiable spaces and Wigner type transforms. J. Math. Anal. Appl. 446, 920–944 (2017)Boiti, C., Jornet, D., Oliaro, A.: The Gabor wave front set in spaces of ultradifferentiable functions. Monatsh. Math. 188(2), 199–246 (2019)Boiti, C., Jornet, D., Oliaro, A.: About the nuclearity of $$\cal{S}_{(M_{p})}$$ and $$\cal{S}_{\omega }$$. In: Boggiatto, P., et al. (eds.) Advances in Microlocal and Time-Frequency Analysis. Applied and Numerical Harmonic Analysis, pp. 121–129. Birkhäuser, Cham (2020)Boiti, C., Jornet, D., Oliaro, A.: Real Paley-Wiener theorems in spaces of ultradifferentiable functions. J. Funct. Anal. 278(4), 108348 (2020)Bonet, J., Meise, R., Melikhov, S.N.: A comparison of two different ways to define classes of ultradifferentiable functions. Bull. Belg. Math. Soc. Simon Stevin 14(3), 425–444 (2007)Braun, R.W., Meise, R., Taylor, B.A.: Ultradifferentiable functions and Fourier analysis. Result. Math. 17, 206–237 (1990)Fernández, C., Galbis, A., Jornet, D.: Pseudodifferential operators on non-quasianalytic classes of Beurling type. Studia Math. 167(2), 99–131 (2005)Fernández, C., Galbis, A., Jornet, D.: Pseudodifferential operators of Beurling type and the wave front set. J. Math. Anal. Appl. 340(2), 1153–1170 (2008)Franken, U.: Weight functions for classes of ultradifferentiable functions. Results Math. 25, 50–53 (1994)Gröchenig, K.: Foundations of Time-Frequency Analysis. Birkhäuser, Boston (2001)Gröchenig, K., Leinert, M.: Wiener’s Lemma for twisted convolution and Gabor frames. J. Am. Math. Soc. 17(1), 1–18 (2004)Gröchenig, K., Zimmermann, G.: Spaces of Test Functions via the STFT. J. Funct. Spaces Appl. 2(1), 25–53 (2004)Heinrich, T., Meise, R.: A support theorem for quasianalytic functionals. Math. Nachr. 280(4), 364–387 (2007)Hörmander, L.: Notions of Convexity. Progress in Mathematics, vol. 127. Birkhäuser, Boston (1994)Janssen, A.J.E.M.: Duality and Biorthogonality for Weyl-Heisenberg Frames. J. Fourier Anal. Appl. 1(4), 403–436 (1995)Komatsu, H.: Ultradistributions I. Structure theorems and a characterization. J. Fac. Sci. Univ. Tokyo Sect IA Math. 20, 25–105 (1973)Langenbruch, M.: Hermite functions and weighted spaces of generalized functions. Manuscripta Math. 119(3), 269–285 (2006)Meise, R., Vogt, D.: Introduction to Functional Analysis. Clarendon Press, Oxford (1997)Petzsche, H.J.: Die nuklearität der ultradistributionsräume und der satz vom kern I. Manuscripta Math. 24, 133–171 (1978)Pietsch, A.: Nuclear Locally Convex Spaces. Springer, Berlin (1972)Pilipović, S., Prangoski, B., Vindas, J.: On quasianalytic classes of Gelfand-Shilov type. Parametrix and convolution. J. Math. Pures Appl. 116, 174–210 (2018)Rodino, L.: Linear Partial Differential Operators in Gevrey Spaces. World Scientific Publishing Co. Inc, River Edge, NJ (1993)Rodino, L., Wahlberg, P.: The Gabor wave front set. Monatsh. Math. 173, 625–655 (2014)Schmets, J., Valdivia, M.: Analytic extension of ultradifferentiable Whitney jets. Collect. Math. 50(1), 73–94 (1999

Identification of T-Cell Antigens Specific for Latent Mycobacterium Tuberculosis Infection

BACKGROUND: T-cell responses against dormancy-, resuscitation-, and reactivation-associated antigens of Mycobacterium tuberculosis are candidate biomarkers of latent infection in humans. METHODOLOGY/PRINCIPAL FINDINGS: We established an assay based on two rounds of in vitro restimulation and intracellular cytokine analysis that detects T-cell responses to antigens expressed during latent M. tuberculosis infection. Comparison between active pulmonary tuberculosis (TB) patients and healthy latently M. tuberculosis-infected donors (LTBI) revealed significantly higher T-cell responses against 7 of 35 tested M. tuberculosis latency-associated antigens in LTBI. Notably, T cells specific for Rv3407 were exclusively detected in LTBI but not in TB patients. The T-cell IFNgamma response against Rv3407 in individual donors was the most influential factor in discrimination analysis that classified TB patients and LTBI with 83% accuracy using cross-validation. Rv3407 peptide pool stimulations revealed distinct candidate epitopes in four LTBI. CONCLUSIONS: Our findings further support the hypothesis that the latency-associated antigens can be exploited as biomarkers for LTBI

Personality and Temperament Correlates of Pain Catastrophizing in Young Adolescents

Pain catastrophizing is generally viewed as an important cognitive factor underlying chronic pain. The present study examined personality and temperament correlates of pain catastrophizing in a sample of young adolescents (N = 132). Participants completed the Pain Catastrophizing Scale for Children, as well as scales for measuring sensitivity of the behavioral inhibition and behavioral activation systems (BIS-BAS), and various reactive and regulative temperament traits. Results demonstrated that BIS, reactive temperament traits (fear and anger-frustration), and perceptual sensitivity were positively related to pain catastrophizing, whereas regulative traits (attention control, inhibitory control) were negatively associated with this cognitive factor. Further, regression analyses demonstrated that only BIS and the temperamental traits of fear and perceptual sensitivity accounted for a unique proportion of the variance in adolescents’ pain catastrophizing scores

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

A miR-200b/200c/429-Binding Site Polymorphism in the 3′ Untranslated Region of the AP-2α Gene Is Associated with Cisplatin Resistance

The transcription factor AP-2α functions as a tumor suppressor by regulating various genes that are involved in cell proliferation and apoptosis. Chemotherapeutic drugs including cisplatin induce post-transcriptionally endogenous AP-2α, which contributes to chemosensitivity by enhancing therapy-induced apoptosis. microRNAs (miRNAs) miR-200b, miR-200c and miR-429 (miR-200b/200c/429) are up-regulated in endometrial and esophageal cancers, and their overexpression correlates with resistance to cisplatin treatment. Using computational programs, we predicted that the 3′ untranslated region (UTR) of AP-2α gene contains a potential miRNA response element (MRE) for the miR-200b/200c/429 family, and the single nucleotide polymorphism (SNP) site rs1045385 (A or C allele) resided within the predicted MRE. Luciferase assays and Western blot analysis demonstrated that the miR-200b/200c/429 family recognized the MRE in the 3′ UTR of AP-2α gene and negatively regulated the expression of endogenous AP-2α proteins. SNP rs1045385 A>C variation enhanced AP-2α expression by disrupting the binding of the miR-200b/200c/429 family to the 3′ UTR of AP-2α. The effects of the two polymorphic variants on cisplatin sensitivity were determined by clonogenic assay. The overexpression of AP-2α with mutant 3′ UTR (C allele) in the endometrial cancer cell line HEC-1A, which has high levels of endogenous miR-200b/200c/429 and low levels of AP-2α protein, significantly increased cisplatin sensitivity, but overexpression of A allele of AP-2α has no significant effects, compared with mock transfection. We concluded that miR-200b/200c/429 induced cisplatin resistance by repressing AP-2α expression in endometrial cancer cells. The SNP (rs1045385) A>C variation decreased the binding of miR-200b/200c/429 to the 3′ UTR of AP-2α, which upregulated AP-2α protein expression and increased cisplatin sensitivity. Our results suggest that SNP (rs1045385) may be a potential prognostic marker for cisplatin treatment

Attentional bias retraining in cigarette smokers attempting smoking cessation (ARTS): study protocol for a double bline randomised controlled trial

YesSmokers attend preferentially to cigarettes and other smoking-related cues in the environment, in what is known as an attentional bias. There is evidence that attentional bias may contribute to craving and failure to stop smoking. Attentional retraining procedures have been used in laboratory studies to train smokers to reduce attentional bias, although these procedures have not been applied in smoking cessation programmes. This trial will examine the efficacy of multiple sessions of attentional retraining on attentional bias, craving, and abstinence in smokers attempting cessation. This is a double-blind randomised controlled trial. Adult smokers attending a 7-session weekly stop smoking clinic will be randomised to either a modified visual probe task with attentional retraining or placebo training. Training will start 1 week prior to quit day and be given weekly for 5 sessions. Both groups will receive 21 mg transdermal nicotine patches for 8–12 weeks and withdrawal-orientated behavioural support for 7 sessions. Primary outcome measures are the change in attentional bias reaction time and urge to smoke on the Mood and Physical Symptoms Scale at 4 weeks post-quit. Secondary outcome measures include differences in withdrawal, time to first lapse and prolonged abstinence at 4 weeks post-quit, which will be biochemically validated at each clinic visit. Follow-up will take place at 8 weeks, 3 months and 6 months post-quit. This is the first randomised controlled trial of attentional retraining in smokers attempting cessation. This trial could provide proof of principle for a treatment aimed at a fundamental cause of addiction.National Institute for Health Research (NIHR) Doctoral Research Fellowship (DRF) awarded to RB (DRF-2009-02-15

The Emergence and Early Evolution of Biological Carbon-Fixation

The fixation of into living matter sustains all life on Earth, and embeds the biosphere within geochemistry. The six known chemical pathways used by extant organisms for this function are recognized to have overlaps, but their evolution is incompletely understood. Here we reconstruct the complete early evolutionary history of biological carbon-fixation, relating all modern pathways to a single ancestral form. We find that innovations in carbon-fixation were the foundation for most major early divergences in the tree of life. These findings are based on a novel method that fully integrates metabolic and phylogenetic constraints. Comparing gene-profiles across the metabolic cores of deep-branching organisms and requiring that they are capable of synthesizing all their biomass components leads to the surprising conclusion that the most common form for deep-branching autotrophic carbon-fixation combines two disconnected sub-networks, each supplying carbon to distinct biomass components. One of these is a linear folate-based pathway of reduction previously only recognized as a fixation route in the complete Wood-Ljungdahl pathway, but which more generally may exclude the final step of synthesizing acetyl-CoA. Using metabolic constraints we then reconstruct a “phylometabolic” tree with a high degree of parsimony that traces the evolution of complete carbon-fixation pathways, and has a clear structure down to the root. This tree requires few instances of lateral gene transfer or convergence, and instead suggests a simple evolutionary dynamic in which all divergences have primary environmental causes. Energy optimization and oxygen toxicity are the two strongest forces of selection. The root of this tree combines the reductive citric acid cycle and the Wood-Ljungdahl pathway into a single connected network. This linked network lacks the selective optimization of modern fixation pathways but its redundancy leads to a more robust topology, making it more plausible than any modern pathway as a primitive universal ancestral form

Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

Background: Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods: To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results: The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1alpha (HIF-1alpha) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion: In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways

Male oxidative stress infertility (MOSI): proposed terminology and clinical practice guidelines for management of idiopathic male infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause